Vitamin D: A new player in non-alcoholic fatty liver disease? - Feb 2015

Vitamin D through its active form 1a-25-dihydroxyvtamin D [1,25(OH)2D] is a secosteroid hormone that plays a key role in mineral metabolism. Recent years have witnessed a significant scientific interest on vitamin D and expanded its actions to include immune modulation, cell differentiation and proliferation and inflammation regulation. As our understanding of the many functions of vitamin D has grown, the presence of vitamin D deficiency has become one of the most prevalent micronutrient deficiencies worldwide. Concomitantly, non-alcoholic fatty liver disease (NAFLD) has become the most common form of chronic liver disease in western countries. NAFLD and vitamin D deficiency often coexist and epidemiologic evidence has shown that both of these conditions share several cardiometabolic risk factors. In this article we provide an overview of the epidemiology and pathophysiology linking NAFLD and vitamin D deficiency, as well as the available evidence on the clinical utility of vitamin D supplementation in NAFLD.

Methods: A total of 514 participants (22 to 79 years old) with normal BMI and liver enzymes were identified for analysis. Abdominal ultrasound was performed to diagnose NAFLD, and the fatty liver index (FLI) was calculated to quantify liver steatosis. Serum 25(OH)D3 levels were determined by an electrochemiluminescence immunoassay.

Conclusion: The present study demonstrated that serum 25(OH)D3 levels were inversely associated with NAFLD, even in subjects with normal total body fat, suggesting a potential role of lower levels of vitamin D in the occurrence and development of NAFLD.

BACKGROUND AND AIMS: We sought to explore associations between serum 25-hydroxyvitamin D [25(OH)D] levels and non-alcoholic fatty liver disease [NAFLD] in an integrated healthcare delivery system in the U.S.
METHODS AND RESULTS: Six hundred and seven NAFLD cases were randomly matched 1:1 with controls for age, sex, race and season of measurement. Conditional logistic regression was used to evaluate if serum 25(OH)D levels were associated with increased odds of NAFLD (diagnosed by ultrasound) after adjusting for body mass index and history of diabetes, renal, peripheral vascular and liver diseases (model 1) and also for hypertension (model 2). Mean (SD) serum 25(OH)D level was significantly lower in the group with NAFLD as compared with that in the matched control group (75±17 vs. 85±20nmol/L [30±7 vs. 34±8ng/mL], P<0.001).
Inadequate 25(OH)D status progressively increased the odds of NAFLD when classified categorically as sufficient (25(OH)D 75nmol/L [>30ng/mL], reference group), insufficient (37-75nmol/L [15-30ng/mL]; adjusted odds ratio [OR]: 2.40, 95% confidence interval [CI]: 0.90-6.34) or deficient (<37nmol/L [<15ng/mL]; adjusted OR: 2.56, 95% CI: 1.27-5.19).

CONCLUSION: Compared with matched controls, patients with NAFLD have significantly decreased serum 25(OH)D levels, suggesting that low 25(OH)D status might play a role in the development and progression of NAFLD.

Background and aims
Non-alcoholic fatty liver disease (NAFLD) and serum 25-hydroxyvitamin D (s25(OH)D) concentrations are both associated with adiposity and insulin resistance (IR) and thus may be pathogenically linked. We aimed to determine the prevalence of vitamin D deficiency in adolescents with NAFLD and to investigate the longitudinal and cross-sectional associations between s25(OH)D concentrations and NAFLD.

Methods
Participants in the population-based West Australian Pregnancy (Raine) Cohort had seasonally-adjusted s25(OH)D concentrations determined at ages 14 and then 17 years. NAFLD was diagnosed at 17 years using liver ultrasonography. Associations were examined after adjusting for potential confounders. Odds ratios (OR) and confidence intervals (CI) are reported per standard deviation in s25(OH)D concentrations.

Results
NAFLD was present in 16% (156/994) of adolescents.
The majority of participants with NAFLD had either

insufficient (51%) or

deficient (17%) vitamin D status.

Lower s25(OH)D concentrations at 17 years were significantly associated with increased risk of NAFLD (OR 0.74, 95%CI 0.56,0.97; p=0.029), after adjusting for sex, race, physical activity, television/computer viewing, body mass index and IR. The effect of s25(OH)D concentrations at 17 years was minimally affected after further adjusting for s25(OH)D concentrations at 14 years (OR 0.76, 95%CI 0.56,1.03; p=0.072).

Conclusions
Lower s25(OH)D concentrations are significantly associated with NAFLD, independent of adiposity and IR. Screening for vitamin D deficiency in adolescents at risk of NAFLD is appropriate, and clinical trials investigating the effect of vitamin D supplementation in the prevention and treatment of NAFLD may be warranted.

Note by VitaminDWiki:Insufficient level of Vitamin D is not defined in the abstract. It may be <20 ng or might be <30 ng

See also web

NAFLD by American Liver foundationWHO IS LIKELY TO HAVE NAFLD? NAFLD tends to develop in people who are overweight or obese or have diabetes, high cholesterol or high triglycerides.
Rapid weight loss and poor eating habits also may lead to NAFLD.
However, some people develop NAFLD even if they do not have any risk factors. NAFLD affects up to 25% of people in the United States.
SYMPTOMS: NAFLD often has no symptoms.
When symptoms occur, they may include fatigue, weakness, weight loss, loss of appetite, nausea, abdominal pain, spider-like blood vessels, yellowing of the skin and eyes (jaundice), itching, fluid build up and swelling of the legs (edema) and abdomen (ascites), and mental confusion.

WikipediaMost patients with NAFLD have few or no symptoms. Patients may complain of fatigue, malaise, and dull right-upper-quadrant abdominal discomfort.
Mild jaundice may be noticed although this is rare. More commonly NAFLD is diagnosed following abnormal liver function tests during routine blood testsPediatric Nonalcoholic Fatty Liver Disease (NAFLD) was first reported in 1983. It is currently the primary form of liver disease among children
VitaminDWiki comment: The first report was just about when vitamin D levels started falling.

HealthlineIn many cases, doctors are not exactly sure what causes fatty liver in people who aren’t alcoholics,
but it has been associated with high blood cholesterol, obesity, and type 2 diabetes.
Fatty liver develops when the body creates too much fat or cannot metabolize fat fast enough.
As a result, the leftover is stored in liver cells where it accumulates to become fatty liver disease.
Eating a high-fat diet does not directly result in fatty liver.

BACKGROUND: Hypovitaminosis D has been recently recognized as a worldwide epidemic. Since vitamin D exerts significant metabolic activities, comprising free fatty acids (FFA) flux regulation from the periphery to the liver, its deficiency may promote fat deposition into the hepatocytes. Aim of our study was to test the hypothesis of a direct association between hypovitaminosis D and the presence of NAFLD in subjects with various degree of insulin-resistance and related metabolic disorders.

METHODS: We studied 262 consecutive subjects referred to the Diabetes and Metabolic Diseases clinics for metabolic evaluation. NAFLD (non-alcoholic fatty liver disease) was diagnosed by upper abdomen ultrasonography, metabolic syndrome was identified according to the Third Report of National Cholesterol Education Program/Adult Treatment Panel (NCEP/ATPIII) modified criteria. Insulin-resistance was evaluated by means of HOMA-IR. Fatty-Liver-Index, a recently identified correlate of NAFLD, was also estimated. Serum 25(OH)vitamin D was measured by colorimetric method.

CONCLUSIONS: Low 25(OH)vitamin D levels are associated with the presence of NAFLD independently from metabolic syndrome, diabetes and insulin-resistance profile.

PMID: 21749681

PDF is attached at the bottom of this page

Vitamin D and NAFLD: Is it more than just an association? (Sept 2013)

Hepatology Vol. 57 Issue 3
Ryan M. Kwok MD1,
Dawn M. Torres MD1,
Stephen A. Harrison MD2,§,*
† Disclaimer The view(s) expressed herein are those of the author(s) and do not reflect the official policy or position of San Antonio Military Medical Center, the U.S. Army Medical Department, the U.S. Army Office of the Surgeon General, the Department of the Army, Department of Defense or the U.S. Government.

Vitamin D is a secosteroid with known effects on calcium homeostasis that has recently been shown to have other significant functions regarding immune modulation, cell differentiation and proliferation, and the inflammatory response. As our understanding of the many functions of vitamin D has grown, the presence of vitamin D deficiency (VDD) has become more evident in Western populations.

Concomitantly, non-alcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease.

NAFLD and VDD are often found together, and while this is not unexpected given their similar associations with obesity and sedentary lifestyle, a growing body of evidence points to a closely linked and potentially causative relationship between VDD and NAFLD. The epidemiologic association between VDD and NAFLD as well as the role of VDD in the pathogenesis of NAFLD and the available evidence on the clinical utility of vitamin D replacement in NAFLD populations will be discussed. (HEPATOLOGY 2013.)

Non-alcoholic fatty liver disease (NAFLD) is one cause of a fatty liver, occurring when fat is deposited (steatosis) in the liver not due to excessive alcohol use. It is related to insulin resistance and the metabolic syndrome and may respond to treatments originally developed for other insulin-resistant states (e.g. diabetes mellitus type 2) such as weight loss metformin and thiazolidinediones. Non-alcoholic steatohepatitis (NASH) is the most extreme form of NAFLD this being regarded as a major cause of cirrhosis of the liver of unknown cause.

The prevalence of non-alcoholic fatty liver disease ranges from 9 to 36.9% of the population in different parts of the world

Approximately 20% of the United States population suffers from non-alcoholic fatty liver, and the prevalence of this condition is increasing.

Symptoms and associationsMost patients with NAFLD have few or no symptoms.Patients may complain of fatigue, malaise, and dull right-upper-quadrant abdominal discomfort.
Mild jaundice may be noticed although this is rare.
More commonly NAFLD is diagnosed following abnormal liver function tests during routine blood tests.
By definition, alcohol consumption of over 20 g/day (about 25 ml/day) excludes the condition.

Nonalcoholic fatty liver disease, also known as nonalcoholic steatohepatitis, or NASH, is a chronic condition that affects 2 to 5 percent of people in the United State. Named to distinguish it from fatty liver disease that occurs in alcoholic patients, NASH involves inflammation or damage to the liver that can be severe and may lead to cirrhosis, liver failure, or liver cancer. The disease often goes hand in hand with diabetes. About 70 percent of people with type 2 diabetes have a fatty liver
Highlights

2% to 5% of population

Strong association with low vitamin D

NAFD associated with diseases which are themselves associated with low vitamin D

insulin resistance

metabolic syndrome

obesity

type II diabetes

high blood pressure

Low vitamin D only increases risk of NAFD by 5% (Odds Ratio = 0.95)

Odds Ratio = 14% for those with BMI < 25 kg/m**2 (from the attached paper, not in the abstract)

A portion of table 5

(unable to discover the vitamin D levels associated with each column)Results are shown as mean±SD. ANOVA test applied. ° Kruskal-Wallis test applied. HOMA-IR, FBG, triglycerides, AST and ALT were considered
as log-values in the analysis. P-values < 0.05 were considered significant.

CONCLUSIONS: Low plasma vitamin D concentration is an independent predictor of the severity of NAFLD.
Further prospective studies demonstrating the impact of vitamin D replacement in NAFLD patients are required.

BACKGROUND/AIMS:
A low vitamin D level has been associated with metabolic syndrome and diabetes. However, an association between a low vitamin D level and nonalcoholic fatty liver disease (NAFLD) has not yet been definitively established. This study aimed to characterize the relationship between a vitamin D level and NAFLD in Korea.
METHODS:
A cross-sectional study involving 6,055 health check-up subjects was conducted. NAFLD was diagnosed on the basis of typical ultrasonographic findings and a history of alcohol consumption.
RESULTS:
The subjects were aged 51.7±10.3 years (mean±SD) and 54.7% were female. NAFLD showed a significant inverse correlation with the vitamin D level after adjusting for age and sex [odds ratio (OR)=0.85, 95% confidence interval (CI)=0.75-0.96]. The age- and sex-adjusted prevalence of NAFLD decreased steadily with increasing vitamin D level [OR=0.74, 95% CI=0.60-0.90, lowest quintile (≤14.4 ng/mL) vs highest quintile (≥28.9 ng/mL), p for trend <0.001]. Multivariate regression analysis after adjusting for other metabolic factors revealed that NAFLD showed a significant inverse correlation with both the vitamin D level (>20 ng/mL) [OR=0.86, 95% CI=0.75-0.99] and the quintiles of the vitamin D level in a dose-dependent manner (p for trend=0.001).
CONCLUSIONS:
The serum level of vitamin D, even when within the normal range, was found to be inversely correlated with NAFLD in a dose-dependent manner. Vitamin D was found to be inversely correlated with NAFLD independent of known metabolic risk factors. These findings suggest that vitamin D exerts protective effects against NAFLD.